Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX 78712, USA.

Abstract

The dopaminergic system originating in the midbrain ventral tegmental area (VTA) has been extensively studied over the past decades as a critical neural substrate involved in the development of alcoholism and addiction to other drugs of abuse. Accumulating evidence indicates that ethanol modulates the functional output of this system by directly affecting the firing activity of VTA dopamine neurons, whereas withdrawal from chronic ethanol exposure leads to a reduction in the functional output of these neurons. This chapter will provide an update on the mechanistic investigations of the acute ethanol action on dopamine neuron activity and the neuroadaptations/plasticities in the VTA produced by previous ethanol experience.

Tonic and phasic DA neuron firing. (A) In vivo single-unit recording of DA neuron firing in an anesthetized rat. A spontaneous burst of APs is shown in the background of low-frequency tonic firing. There is a transient pause of activity before tonic firing recommences. Adapted from . (B) Loose-patch extracellular recording of DA neuron firing in a rat midbrain slice. Iontophoretic application of aspartate was made at the time indicated by the arrow (50 ms). (C) Traces illustrating the effects of the NMDA receptor antagonist AP-5 and the mGluR antagonist MCPG on the phasic burst–pause type of activity evoked by repetitive stimulation of glutamatergic afferents (eight stimuli at 66 Hz; left traces) or aspartate iontophoresis (200 ms; right traces). Also note the tonic pacemaker-like firing before and after the burst–pause. Adapted from .

Ethanol stimulates DA neuron firing. (A) Example traces of single-unit recording of DA neuron firing before (top) and 5 min after i.v. injection of ethanol (bottom) in an awake rat. Adapted from . (B) Representative traces of DA neuron firing recorded with a perforated-patch configuration in a brain slice. Note the effect of ethanol on the membrane potential trajectory during the interspike interval. Adapted from .